A novel GPIHBP1 mutation related to familial chylomicronemia syndrome: A series of cases

• Published in: Atherosclerosis 2021-04, Vol.322, p.31-38
• Main Authors: Lima, Josivan Gomes, Helena C Nobrega, Lucia, Moura Bandeira, Flora Tamires, Pires Sousa, Andre Gustavo, Medeiros de Araujo Macedo, Taisa Barreto, Cavalcante Nogueira, Ana Claudia, Fernandes de Oliveira Filho, Antonio, Alves, Renato Jorge, Costa Gurgel Castelo, Maria Helane, Silva Coelho, Fabiana Maria, Maia, Rayana Elias, Lima, Debora Nobrega, Timoteo, Ana Rafaela de Souza, de Melo Campos, Julliane Tamara Araujo
• Format: Article
• Language: English
• Subjects: Acute Disease; Brazil; Familial chylomicronemia syndrome; Female; GPIHBP1; Humans; Hyperlipoproteinemia Type I - genetics; Hypertriglyceridemia; Lipoprotein Lipase - genetics; Male; Mutation; Pancreatitis - genetics; Receptors, Lipoprotein - genetics; Type 1 hyperlipoproteinemia
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2021.02.020

GPIHBP1 is an accessory protein of lipoprotein lipase (LPL) essential for its functioning. Mutations in the GPIHBP1 gene cause a deficit in the action of LPL, leading to severe hypertriglyceridemia and increased risk for acute pancreatitis. We describe twelve patients (nine women) with a novel homozygous mutation in intron 2 of the GPIHBP1 gene. All patients were from the Northeastern region of Brazil and presented the same homozygous variant located in a highly conserved 3′ splicing acceptor site of the GPIHBP1 gene. This new variant was named c.182-1G > T, according to HGVS recommendations. We verified this new GPIHBP1 variant's effect by using the Human Splicing Finder (HSF) tool. This mutation changes the GPIHBP1 pre-mRNA processing and possibly causes the skipping of the exon 3 of the GPIHBP1 gene, affecting almost 50% of the cysteine-rich Lys6 GPIHBP1 domain. Patients presented with severe hypertriglyceridemia (2351 mg/dl [885–20600]) and low HDL (18 mg/dl [5–41). Four patients (33%) had a previous history of acute pancreatitis. We describe a novel GPIHBP1 pathogenic intronic mutation of patients from the Northeast region of Brazil, suggesting the occurrence of a founder effect. [Display omitted] •GPIHBP1 is a protein that participates in lipid metabolism transporting lipoprotein lipase to the capillary lumen.•GPIHBP1 mutations impair the lipolytic metabolism of triglyceride-rich lipoproteins, significantly increasing triglyceridemia.•We describe a series of patients with severe hypertriglyceridemia resulting from a new homozygous GPIHBP1 mutation.•This new mutation is located in a highly conserved 3′ splicing acceptor site of the GPIHBP1 gene.